Human HTm4 is a hematopoietic cell cycle regulator.

Proper control of cell cycle progression is critical for the constant self-renewal, differentiation, and homeostasis of the hematopoietic system. Cells of all types share the common cell cycle regulators. The different expression patterns of common regulators, in a broad sense, define cell-type or lineage specificity. However, there remains the possibility ...
of hematopoietic cell cycle regulators tailored to the demands of the hematopoietic system. Here we describe a novel protein, HTm4, which serves as a hematopoietic cell cycle regulator. Our data indicate that HTm4 is expressed in hematopoietic tissues and is tightly regulated during the differentiation of hematopoietic stem cells. It binds to cyclin-dependent kinase-associated (CDK-associated) phosphatase-CDK2 (KAP-CDK2) complexes, and the three proteins demonstrate similar patterns of cellular expression in human lymphoid tissues. HTm4 stimulates the phosphatase activity of KAP, and its C-terminal region is required for binding to KAP-CDK2 complexes and the modulation of KAP activity. Overexpression of HTm4 can cause cell cycle arrest at the G(0)/G(1) phase. Thus, HTm4 is a novel hematopoietic modulator for the G(1)-S cell cycle transition.
Mesh Terms:
Amino Acid Sequence, CDC2-CDC28 Kinases, Cell Cycle, Cell Cycle Proteins, Cells, Cultured, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase Inhibitor Proteins, Cyclin-Dependent Kinases, Dual-Specificity Phosphatases, Gene Expression Regulation, Hematopoiesis, Hematopoietic Stem Cells, Humans, Immunohistochemistry, Membrane Proteins, Protein Tyrosine Phosphatases, Protein-Serine-Threonine Kinases, Transfection, Two-Hybrid System Techniques
J. Clin. Invest.
Date: Jan. 01, 2002
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